Zeynep YÜCE, Erdinç YÜKSEL, Melek PEHLİVAN, Ömür Gökmen SEVİNDİK, İnci ALACACIOĞLU, Oğuz ALTUNGÖZ

Polysomy 8 Syndrome: A Distinct Clinical Entity Comprising of Myelomonocytic/Monocytic Lineage Involvement in Acute Leukemia

Purpose: Cytogenetic abnormalities have been proven to be among the most valuable prognostic indicators in leukemia, allowing the stratification of patients in risk groups. We describe a patient diagnosed as AML-M5, with myeloid sarcoma and tetrasomy 8 as the sole chromosomal abnormality. We confirm that the presence of polysomy 8 in myeloid lineage malignancies is associated with a distinct clinical entity comprising of myelomonocytic/monocytic lineage involvement, poor prognosis and high incidence of myeloid sarcoma. In aim to obtain a detailed description of this clinical entity, literature of polysomy 8 cases has been reviewed.Methods: Cytogenetic analysis was performed on bone marrow samples directly after aspiration and following 24 h short term culture. Fluorescence in situ hybridization FISH analyses were performed at complete remission stage on interphase nuclei from bone marrow.Results: Cytogenetic analyses revealed tetrasomy 8 as the sole karyotipic change in all metaphases. The presence of tetrasomy was confirmed with C-MYC 8q24 , AML1/ETO ETO-8q21 and chromosome 8 centromeric probe cocktail.Conclusion: Recognition of the polysomy 8 syndrome will allow for the development of a standardized approach to these patients; as well as stimulating further research into the biology of the disorder that will allow for the development of better therapeutic strategies

Keywords:

Tetrasomy 8, Acute Myeloid Leukemia, AML-M5, Myeloid Sarcoma, Polysomy 8 Syndrome, Cytogenetics,

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Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;114:937–951. [CrossRef]
Grimwade D, Hills RK, Moorman AV, et al.; National Cancer Research Institute Adult Leukaemia Working Group. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010;116:354–365. [CrossRef]
Shaffer LG, Mc Gowan-Jordan J, Schmid M. ISCN 2013: an international system for human cytogenetic nomenclature. Basel: S. Karger; 2013.
Kim J, Park TS, Song J, Lee KA, Lee SG, Cheong JW, Choi JR. Tetrasomy 8 in a patient with acute monoblastic leukemia. Korean J Lab Med 2008;28:262–266. [CrossRef]
Aktas D, Tuncbilek E, Cetin M, Hicsonmez G. Tetrasomy 8 as a primary chromosomal abnormality in a child with acute megakaryoblastic leukemia: a case report and review of the literature. Cancer Genet Cytogenet 2001;126:166–168. [CrossRef]
Sheila N, Sait J, Raza A, Sandberg. Tetrasomy of chromosome 8: An interesting and rare cytogenetic phenomenon in acute nonlymphocytic leukemia. Cancer Genet Cytogenet 1987;27:269– 271. [CrossRef]
Shao J, Zhang L, Semenza JC, Beach B, Smith MT. Tetrasomy 8 detected by interphase cytogenetics in a child with acute lymphocytic leukemia. Cancer Genet Cytogenet 1996;92:135–140. [CrossRef]
de Oliveira FM, Brandão RA, Leite-Cueva SD, et al. Tetrasomy 8 in a patient with chronic lymphocytic leukemia. Cancer Genet Cytogenet 2010;198:166–169. [CrossRef]
Beyer V, Mühlematter D, Parlier V, et al. Polysomy 8 defines a clinico- cytogenetic entity representing a subset of myeloid hematologic malignancies associated with a poor prognosis: report on a cohort of 12 patients and review of 105 published cases. Cancer Genet Cytogenet 2005;160:97–119. [CrossRef]
Shin SY, Koo SH, Kwon KC, et al. Chromosome 8 pentasomy with partial tandem duplication of 11q23 in a case of de novo acute myeloid leukemia. Cancer Genet Cytogenet 2009;194:44–47. [CrossRef]
Kameoka J, Horiuchi T, Miyamura K, et al. Acute monoblastic leukemia with tetrasomy 8. Rinsho Ketsueki 2006;47:770–776.
Makis W, Rakheja R, Lavoie J, Hickeson M. Myeloid Sarcoma and Acute Myelomonocytic Leukemia in an Adolescent with Tetrasomy 8: Staging with (18)F-FDG PET/CT. Nucl Med Mol Imaging 2012;46:119– 124. [CrossRef]
Takahashi T, Tsukuda H, Kimura H, Yoshimoto M, Tsujisaki M. Extramedullary relapse of AML with t(9;11)(p22;q23) associated with clonal evolution from trisomy 8 into tetrasomy 8. Intern Med 2010;49:447–451. [CrossRef]
Tsirigotis P, Papageorgiou S, Abatzis D, et al. Acute myelogenous leukemia with tetrasomy 8 is a disease with a poor prognosis. Cancer Genet Cytogenet 2005;161:78–81. [CrossRef]
Jani Sait SN, Raza A, Sandberg AA. Tetrasomy of chromosome 8: an interesting and rare cytogenetic phenomenon in acute nonlymphocytic leukemia. Cancer Genet Cytogenet 1987;27:269– 271. [CrossRef]
Solé F, de Pablos JM, Woessner S, et al Coexistence of tetrasomy 8 and trisomy 8 in a case with myeloid metaplasia with myelofibrosis. Cancer Genet Cytogenet 1997;94:147–150. [CrossRef]
Ferro MT, Vázquez-Mazariego Y, Ramiro S, et al. Trisomy/ tetrasomy of chromosome 8 and +i(8q) as the sole chromosome abnormality in three adult patients with myelomonocytic leukemia. Cancer Genet Cytogenet 2000;120:163–165. [CrossRef]
Kameoka J, Funato T, Obara Y, et al. Clonal evolution from trisomy into tetrasomy of chromosome 8 associated with the development of acute myeloid leukemia from myelodysplastic syndrome. Cancer Genet Cytogenet 2001;124:159–164. [CrossRef]
Yan J, Marceau D, Drouin R. Tetrasomy 8 is associated with a major cellular proliferative advantage and a poor prognosis. two cases of myeloid hematologic disorders and review of the literature. Cancer Genet Cytogenet 2001;125:14–20. [CrossRef]
Abdelmoula NB, Landman-Parker J, Tourniaire B, et al. An aggressive Ewing sarcoma associated with a new variant translocation, t(4;11;22) (q25;q24;q12), hyperdiploid karyotype, and tetrasomy 8. Cancer Genet Cytogenet 2005;163:186–188. [CrossRef]
Trakhtenbrot L, Neumann Y, Mandel M, et al. In vitro proliferative advantage of bone marrow cells with tetrasomy 8 in Ewing sarcoma. Cancer Genet Cytogenet 1996;90:176–178. [CrossRef]
Lessard M, Herry A, Berthou C, et al. Chromosome 8 tetrasomies and pentasomies--a clonal abnormality closely associated with acute monocytic leukaemia. Leuk Lymphoma 1997;27:127–135. [CrossRef]
Zhang XX, Robinson LJ, Stenzel TT, Qumsiyeh MB. Translocation (15;17)(q22;q21) as a secondary chromosomal abnormality in a case of acute monoblastic leukemia with tetrasomy 8. Cancer Genet Cytogenet 1999;113:9–13. [CrossRef]
Alonso-Dominguez JM, Calbacho M, Talavera M, et al. Cytogenetics findings in a histiocytic sarcoma case. Case Rep Hematol 2012;2012:428279. [CrossRef]
Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer, 2014. Mitelman F, Johansson B, Mertens F, editors. [CrossRef]